Objective To evaluate the value of serum Mac-2 binding protein (M2BP) for assessment of the severity of schisto somiasis-induced liver fibrosis, so as to provide insights into non-invasive diagnosis and disease surveillance of liver fibrosis caused by schistosomiasis. Methods A total of 234 individuals with a history of Schistosoma japonicum infection were sampled from Xinhua Village, Lushan City, Jiangxi Province from 2019 to 2020, and 234 serum samples were collected from all participants. All participants received B-ultrasound examinations of the liver. Serum samples were categorized into four groups (grades 0, Ⅰ, Ⅱ and Ⅲ schistosomiasis-induced liver fibrosis groups) according to B-ultrasound examination results, and then, each group was randomly divided into a receiver operating characteristic (ROC) curve group and an efficacy assessment group at a ratio of 7∶3. Serum M2BP concentration was measured in four groups using the enzyme-linked immunosorbent assay (ELISA), and differences in serum M2BP concentrations were compared with analysis of variance and Spearman correlation analysis. Serum M2BP concentration was subjected to ROC curve analysis among individuals with different grades of schistosomiasis-induced liver fibrosis in the ROC curve group to determine the optimal diagnostic threshold of M2BP concentration at different fibrosis grades, and the area under the ROC curve (AUC) was calculated to evaluate the diagnostic performance. The diagnostic accuracy was verified by comparing the accordance rate and Kappa consistency test in the efficacy assessment group. Results Among 234 serum samples, there were 79 samples with grade 0 schistosomiasis-induced liver fibrosis, 87 samples with Grade Ⅰ, 46 samples with Grade Ⅱ and 22 samples with Grade Ⅲ according to the B-ultrasound examinations. The mean serum M2BP concentrations were (0.40 ± 0.31) [95% confidence interval (CI): (0.33, 0.47)], (0.64 ± 0.48) [95% CI: (0.53, 0.74)], (1.76 ± 0.58) [95% CI: (1.59, 1.93)] μg/mL and (2.56 ± 0.93) [95% CI: (2.14, 2.97)] μg/mL in the four groups, respectively (F = 150.796, P < 0.001), and the severity of schistosomiasis-induced liver fibrosis significantly positively correlated with serum M2BP concentration (rs = 0.715, P < 0. 001). The sample sizes of grades 0, Ⅰ, Ⅱ and Ⅲ schistosomiasis-induced liver fibrosis sera were randomly allocated as follows: 55 versus 24, 61 versus 26, 32 versus 14, and 15 versus 7 in the ROC curve and efficacy assessment groups, respectively, and the serum M2BP concentrations were (0.39 ± 0.29) μg/mL and (0.42 ± 0.36) μg/mL (F = 0.196, P > 0.05), (0.59 ± 0.47) μg/mL and (0.75 ± 0.51) μg/mL (F = 1.967, P > 0.05), (1.73 ± 0.59) μg/mL and (1.85 ± 0.57) μg/mL (F = 0.417, P > 0.05), and (2.46 ± 0.64) μg/mL and (2.76 ± 1.41) μg/mL (F = 0.491, P > 0.05), respectively. ROC curve analysis showed that the optimal diagnostic thresholds of serum M2BP concentration were 0.347 86 μg/mL (AUC = 0.635, P < 0.05), 1.188 83 μg/mL (AUC = 0.938, P < 0.000 1) and 2.021 21 μg/mL (AUC = 0.821, P < 0.000 1) for grade Ⅰ, Ⅱ and Ⅲ schistosomiasis-induced liver fibrosis. In addition, the accordance rates between the optimal diagnostic threshold of serum M2BP and B-ultrasound examinations for predicting grade Ⅰ, Ⅱ and Ⅲ schistosomiasis-induceed liver fibrosis were 69.23%, 85.71% and 71.43% (χ2 = 1.340, P > 0.05), and the overall Kappa consistency test showed moderate consistency [Kappa = 0.608, 95% CI: (0.428, 0.788); Z = 6.609, P < 0.000 1]. Conclusions Serum M2BP may serve as a potential biomarker for assessing moderate to advanced schistosomiasis-induced liver fibrosis; however, its diagnostic value for early-stage schistosomiasis-induced liver fibrosis remains limited.

OBJECTIVE: To investigate the biomechanical characteristics of retrograde tibial nailing (RTN) and distal tibial L-shaped plating in the internal fixation of distal tibial fractures. METHODS: Fourteen fresh adult tibia specimens were selected, comprising 7 males and 7 females aged from 34 to 55 years old. The specimens were randomly divided into experimental group and control group by numerical table method with 7 specimens in each group. RTN was used for internal fixation of distal tibial fractures in the experimental group, and L-shaped plate was used for internal fixation of distal tibial fractures in the control group. The axial compression properties of the two groups of specimens were tested under the pressure of 100, 200, 300, 400, and 500 N after operation, and torsional resistance at torque levels of 1.0, 2.0, 3.0, 4.0, 5.0 N·m. The anti-fatigue performance of the specimens was tested at 500 N pressure for 3 000 and 10 000 cycles. X-ray fluoroscopy was performed to observe whether the the internal fixator was deformed and whether the screw was loosened or broken. RESULTS: When the pressure was 400 N and 500 N, the axial compression displacement of the experimental group was (1.11±0.06) mm and (1.24±0.05) mm, which were smaller than those of the control group (1.21±0.08) mm and (1.37±0.11) mm, and the differences were statistically signific (P<0.05). Under the pressure of 500 N, the axial compression stiffness of the experimental group was (389.24±17.79) N·mm^-1, which was significantly higher than that of the control group (362.37±14.44) N·mm^-1(P<0.05). When the torque was 4 and 5 N·m, the torsion angles of the experimental group were (2.97±0.23) ° and (3.41±0.17) °, which were smaller than those of the control group (3.31±0.28) ° and (3.76±0.20) °, and the differences were statistically significant (P<0.05). When the torque was 5 N·m, the torsional stiffness of the experimental group was (1.48±0.07) N·m per degree, which was higher than that of the control group (1.36±0.06) N·m per degree, and the difference was statistically significant (P<0.05). For the intragroup comparison of fatigue resistance, the differences in axial compression displacement between the two groups were not statistically significant at 3 000 and 10 000 cycles (all P>0.05). When 3 000 times and 10 000 times of compression, the axial compression displacement of the experimental group was (1.38±0.08), (1.43±0.07) mm, which was smaller than that of the control group (1.51±0.10), (1.54±0.08) mm, the differences were statistically significant (P<0.05). In the experimental group, no screw loosening, fracture or internal fixation deformation was found, while in the control group, locking screw loosening occurred in 2 models after 10 000 pressures. CONCLUSION The biomechanical performance of RTN is obviously better than that of the distal tibial L-shaped plate, which provides biomechanical data support for the clinical application of RTN.
Humans ; Female ; Male ; Adult ; Tibial Fractures/physiopathology* ; Middle Aged ; Biomechanical Phenomena ; Bone Plates ; Fracture Fixation, Internal/instrumentation* ; Bone Nails ; Tibia/surgery*

Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory therapy.However,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified.Deoxynyboquinone(DNQ)is a natural small molecule discovered from marine actinomycetes.The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1.DNQ exhibited signif-icant anti-inflammatory properties both in vitro and in vivo.The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α,β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine.DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway.Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation.The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry.DNQ triggered the ubiquitination and subsequent degra-dation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of Nrf2.Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

Objective To explore the mechanism of cinobufotalin regulating phosphatase and tensin homolog(PTEN)and member of wingless MMTV integration site family(Wnt)signaling pathway through microRNA-21(miR-21)on non-small cell lung cancer(NSCLC)cells.Methods HCC827 cells were divided into control group(normal culture),inhibitor-NC group(transfected with miR-21 inhibitor negative control),miR-21 inhibitor group(transfected with miR-21 inhibitor),cinobufacini(Cin)group(0.15 μg·mL-1 cinobufacini),miR-21 mimics group(0.15 μg·mL-1 cinobufacini+miR-21 mimics),OE-PTEN group(0.15 μg·mL-1 cinobufacini+miR-21 mimics+overexpression PTEN plasmid).The mRNA expression levels programmed death ligand-1(PD-L1)were detected by quantitative real-time polymerase chain reaction(qRT-PCR);the number of cell invasion was detected by Transwell chamber method;the expression levels of Wnt/β-catenin pathway-related proteins were detected by Western blot.Results The number of cell invasion in the control group,Cin group,miR-21 mimics group and OE-PTEN group were 121.16±16.43,68.56±11.21,149.30±21.26 and 96.13±13.31,respectively;the protein expression levels of Wnt4 were 1.00±0.13,0.45±0.06,0.93±0.12 and 0.55±0.08,respectively;the protein expression levels ofβ-catenin were 1.00±0.14,0.26±0.04,0.82±0.10 and 0.15±0.03;the mRNA expression levels of PD-L1 were 1.00±0.08,0.71±0.09,1.21±0.11 and 0.70±0.13,respectively.The above indicators of the control group were compared with the Cin group,the above indicators of the Cin group were compared with the miR-21 mimics group,and the above indicators of the miR-21 mimics group were compared with the OE-PTEN group,the differences were statistically significant(all P＜0.05).Conclusion Cinobufotalin may improve the immune function of NSCLC cells,inhibit their invasion and proliferation by down-regulating miR-21 expression to regulate PTEN,Wnt/β-catenin pathway.

Objective To explore the mechanism of cinobufotalin regulating phosphatase and tensin homolog(PTEN)and member of wingless MMTV integration site family(Wnt)signaling pathway through microRNA-21(miR-21)on non-small cell lung cancer(NSCLC)cells.Methods HCC827 cells were divided into control group(normal culture),inhibitor-NC group(transfected with miR-21 inhibitor negative control),miR-21 inhibitor group(transfected with miR-21 inhibitor),cinobufacini(Cin)group(0.15 μg·mL-1 cinobufacini),miR-21 mimics group(0.15 μg·mL-1 cinobufacini+miR-21 mimics),OE-PTEN group(0.15 μg·mL-1 cinobufacini+miR-21 mimics+overexpression PTEN plasmid).The mRNA expression levels programmed death ligand-1(PD-L1)were detected by quantitative real-time polymerase chain reaction(qRT-PCR);the number of cell invasion was detected by Transwell chamber method;the expression levels of Wnt/β-catenin pathway-related proteins were detected by Western blot.Results The number of cell invasion in the control group,Cin group,miR-21 mimics group and OE-PTEN group were 121.16±16.43,68.56±11.21,149.30±21.26 and 96.13±13.31,respectively;the protein expression levels of Wnt4 were 1.00±0.13,0.45±0.06,0.93±0.12 and 0.55±0.08,respectively;the protein expression levels ofβ-catenin were 1.00±0.14,0.26±0.04,0.82±0.10 and 0.15±0.03;the mRNA expression levels of PD-L1 were 1.00±0.08,0.71±0.09,1.21±0.11 and 0.70±0.13,respectively.The above indicators of the control group were compared with the Cin group,the above indicators of the Cin group were compared with the miR-21 mimics group,and the above indicators of the miR-21 mimics group were compared with the OE-PTEN group,the differences were statistically significant(all P＜0.05).Conclusion Cinobufotalin may improve the immune function of NSCLC cells,inhibit their invasion and proliferation by down-regulating miR-21 expression to regulate PTEN,Wnt/β-catenin pathway.

Although it has become a consensus in the field of colorectal surgery to perform radical tumor treatment and functional protection under the minimally invasive concept, there exist many controversies during clinical practice, including the concept of embryonic development of abdominal organs and membrane anatomy, the principle of membrane anatomy related to right hemicolectomy, D3 resection, and identification of the inner boundary. In this paper, we analyzed recently reported literature with high-level evidence and clinical data from the author's hospital to recognize and review the membrane anatomy-based laparoscopic assisted right hemicolectomy for right colon cancer, emphasizing the importance of priority of surgical dissection planes, vascular orientation, and full understanding of the fascial space, and proposing that the surgical planes should be dissected in the parietal-prerenal fascial space, and the incision should be 1 cm from the descending and horizontal part of the duodenum. The surgery should be performed according to a standard procedure with strict quality control. To identify the resection range of D3 dissection, it is necessary to establish a clinical, imaging, and pathological evaluation model for multiple factors or to apply indocyanine green and nano-carbon lymphatic tracer intraoperatively to guide precise lymph node dissection. We expect more high-level evidence of evidence-based medicine to prove the inner boundary of laparoscopic assisted radical right colectomy and a more rigorous consensus to be established.
Humans ; Laparoscopy/methods* ; Colonic Neoplasms/pathology* ; Lymph Node Excision/methods* ; Colectomy/methods* ; Dissection

Purpose: We aimed to analyze the optimal timing of enteral nutrition (EN) in the treatment of sepsis and its effect on sepsis-associated acute kidney injury (SA-AKI.) Materials and Methods: The MIMIC-III database was employed to identify patients with sepsis who had received EN. With AKI as the primary outcome variable, receiver operating characteristic (ROC) curves were utilized to calculate the optimal cut-off time of early EN (EEN). Propensity score matching (PSM) was employed to control confounding effects. Logistic regressions and propensity score-based inverse probability of treatment weighting were utilized to assess the robustness of our findings. Comparisons within the EEN group were performed. Results: 2364 patients were included in our study. With 53 hours after intensive care units (ICU) admission as the cut-off time of EEN according to the ROC curve, 1212 patients were assigned to the EEN group and the other 1152 to the delayed EN group. The risk of SA-AKI was reduced in the EEN group (odds ratio 0.319, 95% confidence interval 0.245–0.413, p<0.001). The EEN patients received fewer volumes (mL) of intravenous fluid (IVF) during their ICU stay (3750 mL vs. 5513.23 mL, p<0.001). The mediating effect of IVF was significant (p<0.001 for the average causal mediation effect). No significant differences were found within the EEN group (0–48 hours vs. 48–53 hours), except that patients initiating EN within 48 hours spent fewer days in ICU and hospital. Conclusion EEN is associated with decreased risk of SA-AKI, and this beneficial effect may be proportionally mediated by IVF volume.

OBJECTIVE: To evaluate the effect of transcutaneous acupoint electrical stimulation (TEAS) at Neiguan (PC 6) on general anesthesia under preserving spontaneous breathing in thoracoscopic lobectomy. METHODS: A total of 66 patients of primary lung cancer undergoing thoracoscopic lobectomy were divided to an observation group (33 cases, 1 case discontinued) and a control group (33 cases). In the observation group, TEAS at Neiguan (PC 6) was used 30 min before anesthesia induction till the end of surgery. The surgery time, maximum value of partial pressure of end-tidal carbon dioxide (P_ETCO₂) and minimum value of oxygen saturation (SpO₂) of the two groups were recorded. The dosage of propofol, sufentanil, remifentanil and dexmedetomidine were analyzed. Separately, before induction (T₀), at the start of surgery (T₁), thoracic exploration (T₂) and lobectomy (T₃), as well as 30 min (T₄) and 60 min (T₅) after lobectomy, the mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR), serum cortisol (Cor) and norepinephrine (NE) were measured. The time of post anesthesia care unit (PACU) stay, ambulation, flatus, chest drainage and the incidence of nausea and vomiting were compared between the two groups. RESULTS: The maximum value of P_ETCO₂, the dosage of propofol and remifentanil in the observation group were lower than those in the control group (P < 0.05, P < 0.01), the minimum value of SpO₂ in the observation group was higher than that of the control group (P < 0.01). At T₁-T₅, the MAP, HR, serum Cor and NE levels in the observation group were all lower than those in the control group (P < 0.05). The ambulation time, the time for the flatus, chest drainage time, and the incidence of nausea and vomiting in the observation group were all lower than those in the control group (P<0.001, P < 0.01). CONCLUSION For the general anesthesia under preserving spontaneous breathing in thoracoscopic surgery, TEAS at Neiguan (PC 6) relieves stress response, reduces opioids dosage and promotes postoperative recovery.
Humans ; Acupuncture Points ; Carbon Dioxide ; Flatulence ; Propofol ; Remifentanil ; Anesthesia, General ; Nausea ; Norepinephrine ; Electric Stimulation

Objectives: To examine the short-term and mid-term effects of surgical treatment of obstructive hypertrophic cardiomyopathy (HCM) in one center. Methods: The perioperative data and short-term follow-up outcomes of 421 patients with obstructive HCM who received surgical treatment at Department of Cardiac Surgery, Zhongshan Hospital, Fudan University from January 2017 to December 2021 were analyzed retrospectively. There were 207 males and 214 females, aged (56.5±11.7) years (range: 19 to 78 years). Preoperative New York Heart Association (NYHA) classification included 45 cases of class Ⅱ, 328 cases in class Ⅲ, and 48 cases in class Ⅳ. Fifty-eight patients were diagnosed with latent obstructive HCM and 257 patients had moderate or more mitral regurgitation with 56 patients suffering from intrinsic mitral valve diseases. All procedures were completed by a multidisciplinary team, including professional echocardiologists involving in preoperative planning for proper mitral valve management strategies and intraoperative monitoring. A total of 338 patients underwent septal myectomy alone, and 59 patients underwent mitral valve surgery along with myectomy. A single transaortic approach was used in 355 patients, and a right atrial-atrial septal/atrial sulcus approach was used in 51 other patients. Long-handled minimally invasive surgical instruments were used for the procedures. Student t test, Wilcoxon rank sum test, χ² test or Fisher exact test were used to compare the data before and after surgery. Results: The aortic cross-clamping time of septal myectomy alone was (34.3±8.5) minutes (range: 21 to 94 minutes). Eighteen patients had intraoperative adverse events and underwent immediate reoperation, including residual obstruction (10 patients), left ventricular free wall rupture (4 patients), ventricular septal perforation (3 patients), and aortic valve perforation (1 patient). Four patients died during hospitalization, and 11 patients developed complete atrioventricular block requiring permanent pacemaker implantation. After discharge, 384 (92.1%) patients received a follow-up visit with a median duration of 9 months. All follow-up patients survived with significantly improved NYHA classifications: 216 patients in class Ⅰ and 168 patients in class Ⅱ (χ²=662.73, P<0.01 as compared to baseline). At 6 months after surgery, follow-up echocardiography showed that the thickness of the ventricular septum ((13.6±2.5) mm vs. (18.2±3.0) mm, t=23.51, P<0.01) and the peak left ventricular outflow tract gradient ((12.0±6.3) mmHg vs. (93.4±19.8) mmHg, 1 mmHg=0.133 kPa, t=78.29, P<0.01) were both significantly lower than baseline values. Conclusion: The construction of the surgical team (including echocardiography experts), proper mitral valve management strategies, identification and management of sub-mitral-valve abnormalities, and application of long-handled minimally invasive surgical instruments are important for the successful implementation of septal myectomy with satisfactory short-and medium-term outcomes.
Male ; Female ; Humans ; Retrospective Studies ; Atrial Fibrillation ; Treatment Outcome ; Cardiomyopathy, Hypertrophic/surgery* ; Mitral Valve Insufficiency/surgery* ; Ventricular Septum

The purpose of this research is to identify the chemical constituents of sea buckthorn leaves extract (SBLE) and explore its hypoglycemic biological activity. SBLE was prepared by hot reflux extraction with 65% ethanol, and its chemical composition was analyzed by ultra-high-performance liquid chromatography-photodiode array-mass spectrometry/mass spectrometry (UHPLC-PDA-MS/MS) system. The animal experiments were compliant with ethical principles for animal use and had been approved by the Animal Experiment Ethics Committee of Jinan University. Mice were injected with streptozocin (STZ) to establish a hyperglycemic animal model, and SBLE (1.5 g·kg^-1) was administered by gavage for 5 weeks. The fasting blood glucose (FBG) and oral glucose tolerance were detected. Normal mice were given SBLE (1.5 g·kg^-1) by intragastric administration for 10 days, and blood was collected from the tail vein to detect the changes in blood glucose within 120 min after sucrose or starch loading. The mucous membrane of the small intestine of mice was taken to detect the activity of α-glucosidase (AG), and the activity of yeast-derived AG incubated with SBLE was evaluated. The glucose uptake by Caco-2 cells treated with SBLE was detected by fluorescence microscopy and cytometry, and the gene expression of sodium-dependent glucose transporter 1 (SGLT1) and glucose transporter 2 (GLUT2) in Caco-2 cells were detected by real-time quantitative PCR (qPCR). A total of 18 compounds were identified, mainly including tannins and flavonoids. SBLE reduced FBG and increased oral glucose tolerance in STZ hyperglycemic mice. SBLE effectively inhibited the increase of blood glucose caused by starch intake in normal mice. SBLE exerted good inhibitory activity on yeast-derived AG (IC₅₀ = 16.94 μg·mL^-1) and small intestinal mucosa AG with an inhibition rate of 15.48%. SBLE (25-100 μg·mL^-1) dose-dependently inhibited glucose uptake by Caco-2 cells, and SBLE significantly reduced the mRNA level of SGLT1 without changing the expression of GLUT2. In conclusion, the UHPLC characteristic fingerprint of SBLE is established with 18 chemical components identified by mass spectrometry, and SBLE exerts hypoglycemic effect by inhibiting the activity of AG and the absorption of glucose by intestinal epithelial cells.